A Phase 1, Single-Administration Pharmacokinetic and Safety Study of Oral and IV Tedizolid Phosphate in Hospitalized Subjects 2 to <12 Years Old
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 主要终点
- Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid Phosphate (Prodrug)
研究概览
简要总结
This is a study to assess the pharmacokinetics (PK) of tedizolid phosphate and its active metabolite, tedizolid, and the safety of tedizolid phosphate following administration of a single IV (Part A) or oral suspension (Part B) administration to hospitalized participants ages 6 to <12 years (Groups 1 and 3, respectively), and 2 to <6 years (Groups 2 and 4, respectively).
详细描述
Part A (IV):
- Group 1 (Cohort 1 and Cohort 2) (6 to <12 years)
- Group 2 (Cohort 1 and Cohort 2) (2 to <6 years)
Part B (Oral Suspension):
- Group 3 (6 to <12 years)
- Group 4 (2 to <6 years)
In Cohort 1 of Group 1 (IV) participants received a single administration of tedizolid phosphate at 5 mg/kg of total body weight. After all participants in Cohort 1 of Group 1 received study drug, a preliminary analysis of the safety and PK data was performed and results were used to select 4 mg/kg as the appropriate dose for Cohort 2 of Group 1 and Group 3, and to select 6 mg/kg as the starting dose for the younger participants, Cohort 1 of Group 2. After all participants in Cohort 1 of Group 2 receive study drug, another preliminary analysis of the safety and PK data will be performed and results will be used to confirm 6 mg/kg as the appropriate dose for Cohort 2 of Group 2. Similarly, the Group 4 dose will be confirmed after data review of Group 3 results.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Receiving prophylaxis for or with a confirmed or suspected infection with Gram-positive bacteria and receiving concurrent antibiotic treatment with Gram-positive antibacterial activity;
- •Weight >5th percentile and <95th percentile based on age;
- •Stable condition as determined from medical history, physical examination, minimally 5-lead electrocardiogram (ECG), vital signs, and clinical laboratory evaluations;
- •Females must be premenarchal, abstinent, or practicing an effective method of birth control;
排除标准
- •History of seizures, other than febrile seizures, clinically significant cardiac arrhythmia, cystic fibrosis, moderate or severe renal impairment, or any physical condition that could interfere with the study results;
- •Recent (3 month) history or current infection with viral hepatitis or other significant hepatic disease;
- •History of drug allergy or hypersensitivity to oxazolidinones;
- •Pregnant or breast feeding;
- •Significant blood loss within 60 days prior to study start;
- •Any acute or chronic condition that would limit the participant's ability to complete and/or participate in this clinical study.
- •Treatment with investigational medicinal product within 30 days before the infusion/dose of study drug.
- •Oral administration of methotrexate, topotecan, irinotecan or rosuvastatin, during administration of oral study drug. Administration during the follow-up period is allowed, as is administration during treatment with IV study drug.
- •Use of monoamine oxidase inhibitors or serotonergic agents including tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin 5 hydroxytryptamine receptor agonists (triptans), meperidine, or buspirone within,14 days prior to study, or planned use while on study.
研究组 & 干预措施
Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 years)
Participants 6 to <12 years of age received a single intravenous infusion of tedizolid phosphate dosed at 5 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate.
干预措施: Tedizolid Phosphate (IV) (Drug)
Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 years)
Participants 6 to <12 years of age received a single intravenous infusion of tedizolid phosphate dosed at 4 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate.
干预措施: Tedizolid Phosphate (IV) (Drug)
Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 years)
Participants 2 to <6 years of age received a single intravenous infusion of tedizolid phosphate dosed at 6 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate.
干预措施: Tedizolid Phosphate (IV) (Drug)
Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 years)
Participants 2 to <6 years of age received a single intravenous infusion of tedizolid phosphate dosed at 3 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate.
干预措施: Tedizolid Phosphate (IV) (Drug)
Group 3: Tedizolid oral 4 mg/kg (6 to <12 years)
Participants 6 to <12 years of age received a single dose of tedizolid phosphate oral suspension dosed at 4 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate.
干预措施: Tedizolid Phosphate (oral suspension) (Drug)
Group 4: Tedizolid oral 3 mg/kg (2 to <6 years)
Participants 2 to <6 years of age received a single dose of tedizolid phosphate oral suspension dosed at 3 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate.
干预措施: Tedizolid Phosphate (oral suspension) (Drug)
结局指标
主要结局
Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid Phosphate (Prodrug)
时间窗: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
Cmax of tedizolid phosphate in participants ages 6 to \<12 years (Group 1) and 2 to \<6 years (Group 2). Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Last Detectable Measurement
时间窗: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
Area under the plasma concentration time curve (AUC) of tedizolid phosphate from time zero to last detectable measurement following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Infinity
时间窗: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
Area under the plasma concentration time curve (AUC) of tedizolid phosphate from time zero to infinity following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid Phosphate (Prodrug)
时间窗: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
Time to reach peak plasma concentration (Tmax) of tedizolid phosphate in participants ages 6 to \<12 years (Group 1) and 2 to \<6 years (Group 2). Tedizolid phosphate concentrations were below the lower limit of quantification in Group 3 and Group 4. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid (the Active Metabolite)
时间窗: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
Time to reach peak plasma concentration (Tmax) of tedizolid (active metabolite) following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity
时间窗: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
Area under the plasma concentration time curve (AUC) of tedizolid (active metabolite) from time zero to infinity following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Terminal Elimination Half-life (T1/2) of Tedizolid (Active Metabolite)
时间窗: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
Terminal elimination half-life (T1/2) of tedizolid (active metabolite) following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Dose Normalized Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity
时间窗: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
The area under the plasma concentration time curve (AUC) of tedizolid (active metabolite) from time zero to infinity following administration of IV or oral dose, normalized to dosage, was calculated. Per protocol, this outcome used pooled groups as follows: The IV Group pooled Groups 1 and 2, who received tedizolid phosphate via intravenous (IV) administration; the Oral Group pooled groups 3 and 4, who received tedizolid phosphate via oral administration. Pharmacokinetic sampling occurred at the following time points: Group 1 (part of the IV Group): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (part of the IV Group): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (part of the Oral Group): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (part of the Oral Group): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Clearance (CL) of Tedizolid Phosphate (Prodrug) in Participants Who Received Tedizolid Phosphate Intravenously (IV)
时间窗: Group 1 (6 to <12 years): Day 1 immediately after infusion and at 1.5, 2, 3, 4, 6, 12, and 24 hours. Group 2 (2 to <6 years): Day 1 immediately after infusion and at 3, 6, 12, 24 and 48 hours.
CL of IV tedizolid phosphate in participants ages 6 to \<12 years (Group 1) and 2 to \<6 years (Group 2).
Clearance (CL/F) of Tedizolid Phosphate in Participants Who Received Oral Tedizolid Phosphate (Prodrug)
时间窗: Group 3 (6 to <12 years): at 1, 2, 3, 4, 6, 8, 12, and 24 hours after the dose; Group 4 (2 to <6 years): at 3, 6, 9, 12, 24 and 48 hours after the dose
CL/F of oral suspension tedizolid phosphate and its active metabolite, tedizolid, in participants ages 6 to \<12 years (Group 3) and 2 to \<6 years (Groups 4).
Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid (the Active Metabolite)
时间窗: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
Maximum observed drug concentration in plasma (Cmax) of tedizolid (active metabolite) following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Last Detectable Measurement
时间窗: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
Area under the plasma concentration time curve (AUC) of tedizolid (active metabolite) from time zero to last detectable measurement following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Terminal Elimination Half-life (T1/2) of Tedizolid Phosphate (Prodrug)
时间窗: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
Terminal elimination half-life (T1/2) of tedizolid phosphate following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Clearance (CL) of Tedizolid (Active Metabolite) in Participants Who Received Tedizolid Phosphate Intravenously (IV)
时间窗: Group 1 (6 to <12 years): Day 1 immediately after infusion and at 1.5, 2, 3, 4, 6, 12, and 24 hours. Group 2 (2 to <6 years): Day 1 immediately after infusion and at 3, 6, 12, 24 and 48 hours.
CL of IV tedizolid phosphate and its active metabolite, tedizolid, in participants ages 6 to \<12 years (Group 1) and 2 to \<6 years (Group 2).
Clearance (CL/F) of Tedizolid (Active Metabolite) in Participants Who Received Oral Tedizolid Phosphate
时间窗: Group 3 (6 to <12 years): at 1, 2, 3, 4, 6, 8, 12, and 24 hours after the dose; Group 4 (2 to <6 years): at 3, 6, 9, 12, 24 and 48 hours after the dose
CL/F of tedizolid, in participants ages 6 to \<12 years (Group 3) and 2 to \<6 years (Groups 4).
次要结局
- Number of Participants Who Experienced at Least One Adverse Event(Up to 9 days)
- Number of Participants Who Discontinued Study Drug Due to an Adverse Event(1 day)
- Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate(Following single oral dose on Day 1)